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Combination therapy using Malaria drugs to treat TB

Date: 01 December 2019 Tags: Miscellaneous

Issue

Researchers have demonstrated that a drug combination that prevents the bacteria from inducing TB drugs toleration mechanism leads to almost complete clearance of the bacteria from the mice lungs in just two months of therapy.

 

Background

Researchers have made an important discovery of the mechanism used by TB bacteria to tolerate TB drugs, which necessitates longer treatment of six-nine months.

 

Details

  • The common notion is that only the non-replicating or slowly metabolising TB bacteria become tolerant to anti-TB drugs but a team found a fraction of the bacteria inside the macrophages was able to tolerate anti-TB drugs even when actively multiplying.

  • They found that using an already approved anti-malaria drug chloroquine in combination with a TB drug isoniazid can almost clear all the bacteria from the lungs of mice and guinea pigs in just eight weeks. In addition, the drug combination also reduces the chances of TB relapse. 

  • Reducing the pH to make it acidic is the first-line of defence by macrophages when infected with pathogens.

  • But the researchers found that instead of controlling the TB bacteria, the mildly acidic pH was actually facilitating a fraction of the bacteria to continue multiplying and develop drug tolerance.

  • They found that anti-TB drugs induce oxidative stress to kill bacteria inside macrophages. However, the drug tolerant bacteria have a remarkable ability to counter oxidative stress.

  • Also, the drug-tolerant bacteria induce efflux pumps to expel antibiotics as an additional mechanism to reduce antibiotic efficacy.

  • Scientists assumed that reverting the pH within macrophages to its normal state could probably make the bacteria sensitive to antibiotics.

  • The chloroquine drug, which is actively used in treating Malaria, neutralises the pH within the macrophages. This prevents the bacteria from inducing the mechanism to protect themselves from oxidative stress.

  • So no drug-tolerant TB bacteria emerge. Once the pH is neutralised, the isoniazid drug is able to eradicate TB from animals.

  • They observed threefold reduction when combined chloroquine with rifampicin and fivefold reduction when they used chloroquine-isoniazid combination, both of which are anti-TB drugs.